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The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis

By A.E. Greijer and E. van der Wall


Apoptosis can be induced in response to hypoxia. The\ud severity of hypoxia determines whether cells become\ud apoptotic or adapt to hypoxia and survive. A hypoxic\ud environment devoid of nutrients prevents the cell\ud undergoing energy dependent apoptosis and cells become\ud necrotic. Apoptosis regulatory proteins are delicately\ud balanced. In solid tumours, hypoxia is a common\ud phenomenon. Cells adapt to this environmental stress, so\ud that after repeated periods of hypoxia, selection for\ud resistance to hypoxia induced apoptosis occurs. These\ud resistant tumours probably have a more aggressive\ud phenotype and may have decreased responsiveness to\ud treatment. The key regulator of this process, hypoxia\ud inducible factor 1 (HIF-1), can initiate apoptosis by\ud inducing high concentrations of proapoptotic proteins,\ud such as BNIP3, and can cause stabilisation of p53.\ud However, during hypoxia, antiapoptotic proteins, such as\ud IAP-2, can be induced, whereas the proapoptotic protein\ud Bax can be downregulated. During hypoxia, an intricate\ud balance exists between factors that induce or counteract\ud apoptosis, or even stimulate proliferation. Understanding\ud the regulation of apoptosis during hypoxia and the\ud mechanisms of resistance to apoptosis might lead to more\ud specific treatments for solid tumours

Topics: Geneeskunde
Year: 2004
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